Insomnia is a common condition which can range from mild to severe and causes people to have trouble falling or staying asleep. The condition may be chronic or acute and leaves the affected subject with little or poor-quality sleep. Lack of sleep may cause other symptoms, such as trouble focusing, anxiety, depression and irritability. One in three adults has insomnia sometimes, and one in ten adults suffers from chronic insomnia.
While acute insomnia is a symptom or side effect of an emotional, neurological, or other medical or sleep disorder, primary or chronic insomnia is its own disorder generally triggered by long-lasting stress or emotional upset.
Lifestyle changes, including better sleep habits, often help relieve acute insomnia. Treatment of chronic insomnia, on the other hand, often requires cognitive-behavioral therapy, which targets the thoughts and actions that can disrupt sleep and focuses on relieving sleep anxiety, and/or the use of short-term or long-term prescription medicines.
Insomnia medicines may often cause side effects, including feeling groggy in the morning, and, rarely, sleep eating, sleep walking, or driving while asleep.
Zaleplon is a short acting, non-benzodiazepine, GABA agonist hypnotic that is indicated for the short-term treatment of insomnia and is commercially available in the US in the form of immediate release 5 mg and 10 mg capsules under the tradename Sonata®.
Zaleplon has a good safety profile. (See Danjou et al. “A comparison of the residual effects of zaleplon and zolpidem following administration 5 to 2 h before awakening” Br. J. Clin. Pharmacol. 1999; 48(3):367-74), and has less effect on memory and psychomotor function compared to other drugs, such as zolpidem and zopiclone, even when given at doses much greater than those therapeutically required for the treatment of insomnia.
Sonata® has a maximum plasma concentration (Tmax) of about 1 h (bioavailability percent F is about 30%). Yet, the drug has a very short half life (T0.5=1 h). Thus, although zaleplon has been shown to decrease the time to sleep onset, it has not been shown to increase total sleep time or decrease the number of awakenings. Because of its poor sleep maintenance capabilities, zaleplon commanded in 2007 only 3% of the US insomnia market.
Accordingly, there is an urgent need in the art to develop drugs for the treatment of chronic insomnia with improved sleep maintenance. The present invention satisfies this need.